AbbVie announced its plans to voluntarily withdraw the FDA’s accelerated approval for Imbruvica in two blood cancer indications — mantle cell lymphoma (MCL) and refractory marginal zone lymphoma (MZL). Imbruvica is an oral Bruton’s tyrosine kinase (BTK) inhibitor that was first approved in 2013. Initially developed by Pharmacyclics, it was acquired by AbbVie in 2015 and jointly marketed with Johnson & Johnson. The drug has had an extensive clinical program with dozens of studies evaluating its efficacy in a number of indications. It was most recently approved by the FDA for the treatment of patients aged one and older with chronic graft-versus-host disease, making it the first and only BTK drug available for pediatric patients. The drug was initially granted FDA approval for MCL and MZL based on the overall response rates observed in two phases 2 clinical trials under the accelerated approval pathway, but its continued approval was dependent on the demonstration of clinical benefits. The phase 3 SHINE study in previously untreated MCL and the phase 3 SELENE study in relapsed or refractory MZL served as confirmatory studies. Following a discussion with the companies regarding the study findings, the FDA recommended that the primary outcomes of phase 3 confirmatory trials for the indications were inadequate to justify conversion to full approval. In one of phase 3 confirmatory trials, Imbruvica met its primary endpoint of progression-free survival but was associated with increased adverse reactions when given in addition to chemotherapy. In the phase 3 SELENE study, which evaluated the drug as a treatment for relapsed MZL, Imbruvica did not meet its primary goal of progression-free survival. In a recent statement, Roopal Thakkar, AbbVie’s senior vice president and chief medical officer said, “While we are disappointed in the outcome of the confirmatory trials for these indications, we remain confident in the benefit/risk profile of Imbruvica for patients living with multiple forms of blood cancer around the world.” This is not the first time that Imbruvica fails to impress for other cancer indications. In 2019, the treatment failed to show statistically significant improvement in progression-free survival (PFS) or overall survival in metastatic pancreatic cancer patients, compared with the combination of a placebo and two chemotherapy agents.